Critical sized diaphyseal long bone defects arising from trauma or infection, tumor, or avascular bone resection are one of the most challenging problems in orthopedic surgery. Numerous surgical techniques have been employed to treat these defects, but with limited success and a large number of complications. For example, the Ilizarov technique of distraction osteogenesis has become a standard of care for the treatment of large bone defects. Despite the success of the Ilizarov technique in treating long bone defects, however, the technique still suffers from several drawbacks, such as long and labor-intensive treatment times, significant demands on patient compliance, discomfort, and high rates of complications. The Ilizarov technique is also ineffective in the most challenging surgical cases where patients do not have sufficient periosteum to regenerate bone around critical sized bone defects, leaving surgeons with few choices to restore form and function of the patient.